Typically, aberrant cell cycle is a hallmark of cancer. A major challenge in oncology treatment is to identify compounds that target specific tumor types in order to minimize toxicity and to maximize efficacy to the targeted tumor.
In the oncology field, it is common to identify tumor types using microscopic histopathological appearance of fixed and stained tumor samples, and to use systems such as the tumor-node-metastasis system to determine the clinical spread of the tumor. This, and other systems, evaluate the size of the tumor, the presence or absence of the tumor in the lymph nodes, and the presence or absence of metastases to assign a stage to the tumor. The tumor type and the stage are then frequently utilized to select appropriate therapy and to determine prognosis for the patient.
E2F transcription factors control the expression of many genes and play a major role during the G1-S transition in the cell cycle. Several assays currently exist that allow for testing of E2F inhibition; however, these assays suffer from several problems.
For example, current assays are frequently invasive, in that they require significant sampling of a tumor tissue. Other assays are not quantitative, that is, they may report a yes or no answer, but are unable to appropriately quantify and measure, in a non-bias manner, the amount or percentage of block of E2F signaling. Furthermore, current assays require that the experiment is terminated at the time of sample retrieval and therefore cannot be utilized to test E2F activity in a temporal manner.
Accordingly, there is a need to identify new methods and materials that are suitable for determining the efficacy of an inhibitor to block E2F signaling in a non-invasive manner and which is quantitative in a non-bias manner so as to properly identify and quantify the amount of block on a particular inhibitor.